PB2028: ACQUIRED Α-THALASSEMIA IN A PATIENT WITH HIGH-RISK MYELODYSPLASTIC SYNDROME AND BONE MARROW FIBROSIS: CASE REPORT AND LITERATURE REVIEW
Authors: Sofia Chissan, Paschalis Evangelidis, Nikolaos Evangelidis, Nikolaos Kotsiou, Eleni Gavriilaki, Sofia Vakalopoulou, Eleni Yfanti, Stamatia Theodoridou
Journal: HemaSphere (2023)

Topic: 10. Myelodysplastic syndromes - Clinical Background: Disorders of hemoglobin synthesis are usually inherited. In some patients with previously normal hematological function, an acquired abnormal pattern of hemoglobin synthesis, with little or significant clinical importance, can be observed primarily seen in patients with malignancy. Acquired α-thalassemia is the dominant acquired red blood disorder, characterized by hypochromic, microcytic anemia, the presence of HbH, and cell inclusion bodies. Acquired α-thalassemia with myelodysplastic syndrome (ATMDS) is a rare subtype of MDS, diagnosed based on the presence of HbH in High-Performance Liquid Chromatography (HPLC) or Capillary Electrophoresis (CE) and typical inclusion bodies H after incubation. It also requires the diagnosis of hematological malignancy and the exclusion of inherited α-thalassemia. The clinical significance of acquired HbH in MDS patients remains unknown. Aims: Here we report a case of a patient with ATMDS. Our goal is to present the diagnostic procedure that we followed to establish the diagnosis of ATMDS. Furthermore, we aim to inform about the pathogenesis and the clinical status of ATMDS. Methods: We performed a full diagnostic work-up for a patient with suspected MDS, including routine laboratory tests, bone marrow aspiration and biopsy, cytogenetics, JAK2 mutation. Upon suspicion of a hemoglobinopathy, we proceeded following a standard scheme that includes hematological analysis, HPLC, CE, and genetic analysis when required. Available data were recorded, along with a literature review about the ATMDS. Results: A 76- year-old male with normocytic anemia was referred to our clinic. After the exclusion of other causes, bone marrow analysis established the diagnosis of MDS with excess blasts (EB-1) and bone marrow fibrosis grade 3. JAK 2 mutation testing was negative. Cytogenetic analysis was not possible due to the insufficient number of metaphases. Upon 2 cycles of azacytidine, the patient gradually developed hypochromic microcytic anemia. Proband’s hematological data were Hb level of 7.4 g/dL, red blood cell count of 3.170x106/ml, mean corpuscular volume 76.7 fL, mean corpuscular Hb 23.4pg, with ferritin level 824 ng/mL, negative sickle cell test. Peripheral blood smear showed anisocytosis, poikilocytosis, hypochromia, microcyttosis and HPLC analysis of hemoglobin (Biorad- Variant) showed Hb A2 1.4% and Hb F 0.5% and Hb H 3.5%. Inclusion bodies (golf ball) after incubation were found positive. This fact and the lack of a family history of thalassemia led to high clinical suspicion of ATMDS. Further genetic analysis was performed after the patient’s informed consent and showed the mutation HBA1:c.300 + 5 G>A in a heterozygous state that has never before been reported with thalassemia phenotypes and therefore, supported the diagnosis of ATMDS and the patient continues treatment with azacytidine and remains in morphologic remission. Based on the literature review, it is noteworthy that ATMDS is more common in MDS patients with microcytic anemia. Case series of ATMDS have reported inactivating somatic mutations of the ATRX gene, which is a trans-acting chromatin-associated factor. This mechanism results in the downregulation and reduced expression of the a-globin gene. The mechanism involves deletions of a-globin gene cluster at chromosome 16. Bone marrow fibrosis that was found in our patient has been reported only in one patient with ATMDS before. Summary/Conclusion: The diagnosis of ATMDS should be suspected in every older patient with MDS combined with newly onset of hypochromic microcytic anemia and absence of iron deficiency. Keywords: MDS, Myelodysplastic syndrome